Chronic intermittent hypoxia enhances glycinergic inhibition in nucleus tractus solitarius

Shuping Jia, Nataliya Rybalchenko, Kishor Kunwar, George E. Farmer, Joel T. Little, Glenn M. Toney, J. Thomas Cunningham

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Chronic intermittent hypoxia (CIH), an animal model of sleep apnea, has been shown to alter the activity of second-order chemoreceptor neurons in the caudal nucleus of the solitary tract (cNTS). Although numerous studies have focused on excitatory plasticity, few studies have explored CIH-induced plasticity impacting inhibitory inputs to NTS neurons, and the roles of GABAergic and glycinergic inputs on heightened cNTS excitability following CIH are unknown. In addition, changes in astrocyte function may play a role in cNTS plasticity responses to CIH. This study tested the effects of a 7-day CIH protocol on miniature inhibitory postsynaptic currents (mIPSCs) in cNTS neurons receiving chemoreceptor afferents. Normoxia-treated rats primarily displayed GABA mIPSCs, whereas CIH-treated rats exhibited a shift toward combined GABA/glycine-mediated mIPSCs. CIH increased glycinergic mIPSC amplitude and area. This shift was not observed in dorsal motor nucleus of the vagus neurons or cNTS cells from females. Immunohistochemistry showed that strengthened glycinergic mIPSCs were associated with increased glycine receptor protein and were dependent on receptor trafficking in CIH-treated rats. In addition, CIH altered astrocyte morphology in the cNTS, and inactivation of astrocytes following CIH reduced glycine receptor-mediated mIPSC frequency and overall mIPSC amplitude. In cNTS, CIH produced changes in glycine signaling that appear to reflect increased trafficking of glycine receptors to the cell membrane. Increased glycine signaling in cNTS associated with CIH also appears to be dependent on astrocytes. Additional studies will be needed to determine how CIH influences glycine receptor expression and astrocyte function in cNTS.

Original languageEnglish (US)
Pages (from-to)1383-1394
Number of pages12
JournalJournal of neurophysiology
Volume128
Issue number6
DOIs
StatePublished - Dec 2022

Keywords

  • GABA
  • astrocytes
  • chemoreceptor
  • protein trafficking

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology

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